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Prion Diseases, HIV-1 Associated Neurocognitive Disorders, and Alzheimer’s Disease: Implications for Protein Misfolding

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Global Virology I - Identifying and Investigating Viral Diseases

Abstract

Protein misfolding is a common feature of several neurodegenerative diseases including prion disease, Alzheimer’s disease (AD), and certain forms of HIV associated neurocognitive disorders (HAND). In classical prion disease the cellular prion protein, PrPC, after partial misfolding, converts into a protease-resistant disease-associated isoform, PrPSc, which aggregates in the brain and forms deposits that are associated with the neurodegeneration. Although the phenomenon of PrPC to PrPSc conversion does not occur in HIV infection, protein misfolding in the course of HIV infection has been noted in several preclinical and clinical reports in the form of self-assembling misfolded tau and amyloid-beta (Aβ) proteins. In addition, the misfolding of these proteins are hallmark pathologies of AD. Biomarkers as indicators for the progression of AD and HAND are in need. In this chapter we examine PrPc, Aβ, and, tau and their association with prion biology, protein misfolding, and the possible use of all three proteins for diagnostic and/or prognostic clinical use.

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Acknowledgements

B.G. is supported by NIMH/NIH grant (1R01MH098737-02) (PI). The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, 3515 E. Fletcher Ave., MDT14, Tampa, FL, 33613, USA

    Brian Giunta M.D., Ph.D.

  2. Multiple Sclerosis and Stroke, Department of Neurology, LSUHSC-S, 1501 Kings Highway, Shreveport, LA, 71130, USA

    Alireza Minagar M.D., F.A.A.N., F.A.N.A.

  3. Medical Affairs, School of Medicine, University of Texas Rio Grande Valley, 2102 Treasure Hills Boulevard, Harlingen, TX, 78552, USA

    Francisco Fernandez M.D.

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  1. Brian Giunta M.D., Ph.D.
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  3. Francisco Fernandez M.D.
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Correspondence to Brian Giunta M.D., Ph.D. .

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Editors and Affiliations

  1. Division of Infectious Diseases and International Medicine, USF Morsani College of Medicine, Tampa, Florida, USA

    Paul Shapshak

  2. Infectious Diseases and International He, USF Morsani College of Medicine, Tampa, Florida, USA

    John T. Sinnott

  3. Division of Infectious Diseases and Inte, USF Morsani College of Medicine, Tampa, Florida, USA

    Charurut Somboonwit

  4. C.W. Bill Young Center for Biodefense & Emerging Infectious Diseases, NIH-NIAID Div. Clinical Research, Frederick, Maryland, USA

    Jens H. Kuhn

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Giunta, B., Minagar, A., Fernandez, F. (2015). Prion Diseases, HIV-1 Associated Neurocognitive Disorders, and Alzheimer’s Disease: Implications for Protein Misfolding. In: Shapshak, P., Sinnott, J., Somboonwit, C., Kuhn, J. (eds) Global Virology I - Identifying and Investigating Viral Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2410-3_22

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